A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.

The active metabolite of FOLIC ACID. Leucovorin is used principally as an antidote to FOLIC ACID ANTAGONISTS.

Antimetabolites that are useful in cancer chemotherapy.

The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.

An oxidoreductase involved in pyrimidine base degradation. It catalyzes the catabolism of THYMINE; URACIL and the chemotherapeutic drug, 5-FLUOROURACIL.

Organic compounds which contain platinum as an integral part of the molecule.

Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.

Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.

An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.

An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.

The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.

An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.

An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.

An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.

Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

A malignant epithelial tumor with a glandular organization.

An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.

5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.

The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.

Tumors or cancer of the COLON.

Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.

Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.

Congener of FLUOROURACIL with comparable antineoplastic action. It has been suggested especially for the treatment of breast neoplasms.

An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.

Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)

A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.

4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.

Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.

Tumors or cancer of the STOMACH.

Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.

Tumors or cancer of the RECTUM.

An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)

Substances that inhibit or prevent the proliferation of NEOPLASMS.

The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.

Tumors or cancer of the human BREAST.

The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.

Regional infusion of drugs via an arterial catheter. Often a pump is used to impel the drug through the catheter. Used in therapy of cancer, upper gastrointestinal hemorrhage, infection, and peripheral vascular disease.

INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.

Tumors or cancer of the LIVER.

A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.

5-Bromo-2,4(1H,3H)-pyrimidinedione. Brominated derivative of uracil that acts as an antimetabolite, substituting for thymine in DNA. It is used mainly as an experimental mutagen, but its deoxyriboside (BROMODEOXYURIDINE) is used to treat neoplasms.

Agents counteracting or neutralizing the action of POISONS.

The action of a drug in promoting or enhancing the effectiveness of another drug.

A fluorinated cytosine analog that is used as an antifungal agent.

The relationship between the dose of an administered drug and the response of the organism to the drug.

The adaptation of therapeutic approaches such as pharmacological (DRUG CHRONOTHERAPY), surgical, radiological, or physical to the known variations in biological RHYTHMICITY, such as CIRCADIAN RHYTHMS. The treatment is aimed at supporting normal rhythms, or modifying the timing of therapy to achieve maximal efficacy and minimal adverse effect.

A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.

A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)

A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.

Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)

Tumors or cancer of the ESOPHAGUS.

The key substance in the biosynthesis of histidine, tryptophan, and purine and pyrimidine nucleotides.

Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.

An INFLAMMATION of the MUCOSA with burning or tingling sensation. It is characterized by atrophy of the squamous EPITHELIUM, vascular damage, inflammatory infiltration, and ulceration. It usually occurs at the mucous lining of the MOUTH, the GASTROINTESTINAL TRACT or the airway due to chemical irritations, CHEMOTHERAPY, or radiation therapy (RADIOTHERAPY).

Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.

A decrease in the number of NEUTROPHILS found in the blood.

Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.

An enzyme that catalyzes the transfer of 2-deoxy-D-ribose from THYMIDINE to orthophosphate, thereby liberating thymidine.

An enzyme which catalyzes the deamination of CYTOSINE resulting in the formation of URACIL. It can also act on 5-methylcytosine to form THYMIDINE.

Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.

Injections made into a vein for therapeutic or experimental purposes.

Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).

Antagonist of urate oxidase.

An autosomal recessive disorder affecting DIHYDROPYRIMIDINE DEHYDROGENASE and causing familial pyrimidinemia. It is characterized by thymine-uraciluria in homozygous deficient patients. Even a partial deficiency in the enzyme leaves individuals at risk for developing severe 5-FLUOROURACIL-associated toxicity.

An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.

The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.

A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum.

A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.

Uracil nucleotides which contain deoxyribose as the sugar moiety.

A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.

One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.

A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.

An enzyme that catalyzes the transfer of ribose from uridine to orthophosphate, forming uracil and ribose 1-phosphate.

The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)

The giving of drugs, chemicals, or other substances by mouth.

A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.

A cell line derived from cultured tumor cells.

Radiotherapy given to augment some other form of treatment such as surgery or chemotherapy. Adjuvant radiotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride (FLUORIDES) to prevent dental caries.

2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies.

Elements of limited time intervals, contributing to particular results or situations.

Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.

Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.

An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.

The penultimate step in the pathway of histidine biosynthesis. Oxidation of the alcohol group on the side chain gives the acid group forming histidine. Histidinol has also been used as an inhibitor of protein synthesis.

Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.

A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)

Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.

A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.

The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10.

The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.

Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.

Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

The total amount of radiation absorbed by tissues as a result of radiotherapy.

Antitumor alkaloid isolated from Vinca rosea. (Merck, 11th ed.)

The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.

Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.

Treatment that combines chemotherapy with radiotherapy.

The area covering the terminal portion of ESOPHAGUS and the beginning of STOMACH at the cardiac orifice.

Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.

Therapeutic act or process that initiates a response to a complete or partial remission level.

Any surgical procedure for treatment of glaucoma by means of puncture or reshaping of the trabecular meshwork. It includes goniotomy, trabeculectomy, and laser perforation.

New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.

The forcible expulsion of the contents of the STOMACH through the MOUTH.

A subnormal level of BLOOD PLATELETS.

The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.

Catalyze the hydrolysis of nucleosides with the elimination of ammonia.

An amino acid formed in vivo by the degradation of dihydrouracil and carnosine. Since neuronal uptake and neuronal receptor sensitivity to beta-alanine have been demonstrated, the compound may be a false transmitter replacing GAMMA-AMINOBUTYRIC ACID. A rare genetic disorder, hyper-beta-alaninemia, has been reported.

The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)

Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.

Tumors or cancer of the ANAL CANAL.

A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.

Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.

Experimental transplantation of neoplasms in laboratory animals for research purposes.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

Derivatives of acetic acid with one or more fluorines attached. They are almost odorless, difficult to detect chemically, and very stable. The acid itself, as well as the derivatives that are broken down in the body to the acid, are highly toxic substances, behaving as convulsant poisons with a delayed action. (From Miall's Dictionary of Chemistry, 5th ed)

A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.

Disorders of the blood and blood forming tissues.

An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.

Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.